Roles of Drinking Pattern and Type of Alcohol Consumed in Coronary Heart Disease in Men
Kenneth J. Mukamal, M.D., M.P.H., Katherine M. Conigrave, M.B., B.S., Ph.D., Murray A. Mittleman, M.D., Dr.P.H., Carlos A. Camargo, Jr., M.D., Dr.P.H., Meir J. Stampfer, M.D., Dr.P.H., Walter C. Willett, M.D., Dr.P.H., and Eric B. Rimm, Sc.D.
Background Although moderate drinking confers a decreased riskof myocardial infarction, the roles of the drinking patternand type of beverage remain unclear.
Methods We studied the association of alcohol consumption withthe risk of myocardial infarction among 38,077 male health professionalswho were free of cardiovascular disease and cancer at base line.We assessed the consumption of beer, red wine, white wine, andliquor individually every four years using validated food-frequencyquestionnaires. We documented cases of nonfatal myocardial infarctionand fatal coronary heart disease from 1986 to 1998.
Results During 12 years of follow-up, there were 1418 casesof myocardial infarction. As compared with men who consumedalcohol less than once per week, men who consumed alcohol threeto four or five to seven days per week had decreased risks ofmyocardial infarction (multivariate relative risk, 0.68 [95percent confidence interval, 0.55 to 0.84] and 0.63 [95 percentconfidence interval, 0.54 to 0.74], respectively). The riskwas similar among men who consumed less than 10 g of alcoholper drinking day and those who consumed 30 g or more. No singletype of beverage conferred additional benefit, nor did consumptionwith meals. A 12.5-g increase in daily alcohol consumption overa four-year follow-up period was associated with a relativerisk of myocardial infarction of 0.78 (95 percent confidenceinterval, 0.62 to 0.99).
Conclusions Among men, consumption of alcohol at least threeto four days per week was inversely associated with the riskof myocardial infarction. Neither the type of beverage nor theproportion consumed with meals substantially altered this association.Men who increased their alcohol consumption by a moderate amountduring follow-up had a decreased risk of myocardial infarction.
Important questions remain about the effect of alcohol consumptionon coronary heart disease. Among these are the roles that thetype of beverage consumed, the pattern of drinking, and theconsumption of alcohol with meals have in modifying the apparentbenefits of moderate alcohol consumption.1 Furthermore, moststudies have used single measurements of alcohol use and hencehave not assessed the importance of updating alcohol intakeor the effect of changes in consumption over time.
Although the consumption of wine in particular has been hypothesizedto be associated with a lower risk of cardiovascular disease,2systematic reviews differ about the specific effects of beer,wine, and liquor.2,3,4 Likewise, an episodic pattern of drinking,with alcohol consumption concentrated over a few days, confersa higher risk of myocardial infarction,5,6,7 but few studieshave sought to clarify the relative roles of the quantity andfrequency of alcohol consumption or consumption with meals.
To address these questions, we extended our analysis of datafrom the Health Professionals Follow-up Study to 12 years, havingpreviously reported on alcohol use and coronary heart diseaseafter 2 years.8
Methods
The Health Professionals Follow-up Study includes 51,529 U.S.male dentists, veterinarians, optometrists, osteopathic physicians,and podiatrists 40 to 75 years of age who returned a mailedquestionnaire regarding diet and medical history in 1986. Participantsreturn follow-up questionnaires every two years to update informationon exposures and current illnesses. At base line, we excluded5528 men who reported a history of myocardial infarction, angina,stroke, transient ischemic attack, claudication, or cancer (otherthan nonmelanoma skin cancer); 1703 men whose data on alcoholconsumption were missing; 202 men whose questionnaires had othertechnical problems; and 6019 men who currently consumed no alcoholbut reported having consumed alcohol in the preceding 10 years.A total of 38,077 men were therefore included in this analysis.
We assessed average alcohol consumption with a semiquantitativefood-frequency questionnaire, which included separate questionsabout beer, white wine, red wine, and liquor. We standardizedportions as a 12-oz (355-ml) bottle or can of beer, a 4-oz (118-ml)glass of wine, and a shot of liquor. For each beverage, participantsreported their usual average consumption in the preceding year,with nine response categories. We determined alcohol intakeby multiplying the consumption of each beverage by its ethanolcontent (12.8 g for beer, 11.0 g for wine, and 14.0 g for liquor)9and summing all beverages. This process was repeated in 1990and 1994, and a similar question about light beer (containing11.3 g of ethanol) was added in 1994. We categorized daily ethanolintake in grams into seven categories: none, 0.1 to 4.9, 5.0to 9.9, 10.0 to 14.9, 15.0 to 29.9, 30.0 to 49.9, and 50.0 gor more.8
We assessed the validity of self-reported alcohol consumptionby comparing estimates from the food-frequency questionnairewith two seven-day dietary records among 127 participants whoreturned questionnaires in 1986 and 1987.10 The Spearman correlationcoefficients between alcohol use assessed on the basis of thefirst and second questionnaires and dietary records were 0.83and 0.86, respectively.
In 1986, men reported the number of days per week that theytypically drank any alcohol, with five response categories.The correlation coefficient between drinking frequency withthe use of this measure and dietary records was 0.79.11 To determinethe usual quantity of alcohol consumed per drinking day, wedivided average weekly alcohol consumption (from the food-frequencyquestionnaire) by the number of drinking days per week. In 1994,men reported the proportion of their alcohol that was consumedwith meals in four response categories.
We confirmed a reported myocardial infarction if it met WorldHealth Organization criteria, including the presence of symptomsand either typical electrocardiographic changes or elevatedcardiac enzyme levels.12 We included probable myocardial infarctionswhen we could not obtain medical records but the participantrequired hospitalization and supplementary correspondence corroboratedthe diagnosis.
We confirmed deaths when reported by families, postal officials,or the National Death Index, with a combined follow-up rateexceeding 98 percent.13 Fatal coronary heart disease includedfatal myocardial infarction that was confirmed by hospital recordsor, if coronary heart disease was listed as the cause of deathon the death certificate, was the most plausible cause and ifevidence of previous coronary heart disease was available. Weincluded sudden death from cardiac causes, defined as deathwithin one hour after the onset of symptoms in a man with noprevious serious illness and no other plausible cause. Physiciansreviewing medical records were unaware of participants' reportedalcohol intake.
We calculated person-years from the date of return of the 1986questionnaire to the date of the first coronary heart diseaseevent, death, or January 31, 1998. We estimated relative riskswith cumulative incidence ratios, adjusted for age in five-yearcategories and smoking in six categories. In multivariate analyses,we used pooled logistic regression14 to control for age; smokingstatus; quintiles of body-mass index (the weight in kilogramsdivided by the square of the height in meters); use or nonuseof aspirin; physical exertion (in five categories); presenceor absence of hypertension, diabetes, and a parental historyof premature myocardial infarction; energy intake (in quintiles);and energy-adjusted intakes of vitamin E, folate, saturatedfat, trans fatty acids, and dietary fiber (in quintiles). Dietaryvariables were updated every four years, and other covariatesevery two years. We assigned missing variables their valuesfrom the previous questionnaire.
For base-line alcohol consumption, we assessed the risk of subsequentmyocardial infarction according to a single estimate of alcoholconsumption. In updated analyses, we prospectively assessedthe risk of myocardial infarction in four-year increments, basedon alcohol consumption in the preceding questionnaire. We assessedthe risk associated with individual types of beverages usingupdated intake, controlling for standard covariates and theintake of the other beverages. To assess changes in alcoholuse, we determined whether the change from 1986 to 1990 predictedthe risk of myocardial infarction from 1990 to 1994 and whetherthe change from 1990 to 1994 predicted the risk from 1994 to1998.
Results
Base-Line Characteristics
At base line, increasing alcohol consumption was positivelyassociated with smoking, hypertension, and hypercholesterolemia(Table 1). Among men who drank, the amount consumed per drinkingday and the frequency of use were moderately correlated (Spearmancorrelation coefficient, 0.47; P<0.001). Beer and liquorwere consumed in greatest quantities and correlated most closelywith the frequency of drinking (Spearman correlation coefficient,0.32 for red wine, 0.39 for white wine, 0.51 for beer, and 0.61for liquor; P<0.001 for all).
Table 1. Base-Line Characteristics of 38,077 U.S. Male Health Professionals, 40 to 75 Years of Age, According to Alcohol Consumption.
Average Alcohol Consumption
We documented 1418 cases of myocardial infarction during follow-up.We found a graded, inverse relation between updated alcoholconsumption and the risk of myocardial infarction (Table 2),with a similar risk among men who abstained and men who werevery light drinkers (0.1 to 4.9 g daily). Using base-line alcoholconsumption, we found that the relative risks were somewhatweaker although still statistically significant. To minimizethe possibility that alcohol consumption had changed in responseto subclinical disease, we excluded the first four years offollow-up, which had little effect. Our results were also unchangedwhen we excluded hypertension as a covariate or restricted theanalyses to men who reported no change in their alcohol consumptionduring the 10 years before enrollment (data not shown).
Table 2. Relative Risk of Nonfatal, Fatal, and Any Myocardial Infarction among 38,077 U.S. Male Health Professionals, According to Updated or Base-Line Alcohol Consumption.
The association of alcohol consumption with myocardial infarctionwas similar for fatal and nonfatal events (Table 2). Alcoholconsumption was inversely associated with the risk of undergoinga coronary revascularization procedure, with the lowest riskamong those who consumed 50 g or more of alcohol daily (adjustedrelative risk, 0.59; 95 percent confidence interval, 0.43 to0.81; P for trend <0.001).
Pattern of Alcohol Consumption
The frequency of alcohol consumption was strongly inverselyassociated with the risk of myocardial infarction (Table 3).To assess the relative effects of the quantity and frequencyof alcohol consumption, we subdivided the categories of frequencyaccording to the amount of alcohol consumed per drinking day.We found consistently similar risks within categories of frequency,regardless of the amount of alcohol consumed per drinking day.
Table 3. Relative Risks of Myocardial Infarction among 38,077 U.S. Male Health Professionals According to the Base-Line Frequency of Alcohol Consumption and the Quantity of Ethanol Consumed per Drinking Day.
We next compared a frequency of alcohol use of less than threetimes per week with a weekly frequency of three or more timeswithin narrow categories of average alcohol consumption. Amongmen who consumed 0.1 to 4.9, 5.0 to 9.9, 10.0 to 14.9, 15.0to 29.9, or 30.0 to 49.9 g of alcohol per day on average, morefrequent use consistently predicted a reduced risk, with adjustedrelative risks of 0.66 (95 percent confidence interval, 0.37to 1.18), 0.77 (95 percent confidence interval, 0.57 to 1.03),0.72 (95 percent confidence interval, 0.52 to 1.01), 0.74 (95percent confidence interval, 0.44 to 1.23), and 0.76 (95 percentconfidence interval, 0.18 to 3.21), respectively. The inclusionof both the frequency and average quantity of consumption (inseven categories) in a single model did not change the relativerisks associated with the frequency of use, but it markedlyattenuated the estimated effect of the quantity of consumption,with relative risks for myocardial infarction ranging from 1.06to 1.20.
The inverse association between the frequency of alcohol consumptionand the risk of myocardial infarction was similar among menin 10-year age groups from 40 to 49 years to 70 to 79 years(data not shown), including men 40 to 49 years of age who reportedno change in their alcohol consumption in the 10 years beforeenrollment. The use or nonuse of aspirin and the body-mass indexalso did not modify the association of the frequency of alcoholuse with the risk of myocardial infarction.
Type of Beverage
We found inverse relations between the risk of myocardial infarctionand consumption of the four types of beverage, with similarrelative risks at levels of consumption of at least 15.0 g ofalcohol daily (Table 4). The associations were strongest forbeer and liquor, intermediate for white wine, and weakest forred wine. Multivariate adjustment weakened the association ofmyocardial infarction with wine consumption but strengthenedthe associations with beer and liquor consumption.
Table 4. Relative Risks of Myocardial Infarction (MI) among 38,077 U.S. Male Health Professionals, According to the Type of Alcoholic Beverage Consumed.
Timing of Alcohol Intake with Respect to Meals
Of the 20,986 eligible men who reported their alcohol intakewith respect to meals in 1994, 43 percent consumed less than25 percent of their overall intake with meals, 22 percent consumed25 to 74 percent with meals, 24 percent consumed 75 to 100 percentwith meals, and 11 percent did not drink. Among men who consumed5.0 to 29.9 g of alcohol daily, drinking 25 to 74 percent ofthe total with meals and drinking at least 75 percent of thetotal with meals were associated with relative risks of 0.66(95 percent confidence interval, 0.40 to 1.09) and 1.21 (95percent confidence interval, 0.81 to 1.82), respectively, ascompared with drinking less than 25 percent of the total withmeals (P for trend, 0.51). The relative effect of alcohol wassimilar among men with different patterns of consumption withmeals (Table 5).
Table 5. Multivariate Relative Risk of Myocardial Infarction (MI) among 20,986 U.S. Male Health Professionals, According to Alcohol Consumption and the Proportion of Alcohol Consumed with Meals in 1994.
Change in Consumption Over Time
Among men who were free of cardiovascular disease or cancerin 1994, mean daily alcohol consumption declined from 13.1 gin 1986 to 12.0 g in 1994 (Pearson r=0.69, P<0.001). Menwho substantially decreased their consumption had a higher prevalenceof diabetes and symptoms triggering a visit to a physician,and men who substantially increased consumption had a lowerprevalence of hypercholesterolemia (Table 6).
Table 6. Characteristics of 25,692 U.S. Male Health Professionals, According to Average Alcohol Consumption in 1986 and 1994.
As compared with consumption that remained constant or increasedby less than 5.0 g, an increase of 5.0 to 9.9 g was not associatedwith a decreased risk of myocardial infarction (relative risk,1.05; 95 percent confidence interval, 0.72 to 1.55), but anincrease of at least 10.0 g was (relative risk, 0.55; 95 percentconfidence interval, 0.33 to 0.91). Among men whose consumptionremained stable or increased, a 12.5-g increase in daily alcoholconsumption (as a linear variable) was associated with a relativerisk of myocardial infarction of 0.78 (95 percent confidenceinterval, 0.62 to 0.99). Conversely, among men whose consumptionwas stable or decreased during follow-up, a 12.5-g decreasein daily alcohol intake was associated with a nonsignificanttrend toward a higher risk of infarction (relative risk, 1.10;95 percent confidence interval, 0.92 to 1.31), with similarrisks among men whose consumption decreased by 5.0 to 9.9 gper day and those with a decrease of 10.0 g or more per day.
Discussion
Among these 38,077 men, alcohol consumption was consistentlyassociated with a lower risk of coronary heart disease, regardlessof the type of beverage, the proportion consumed with meals,or the type of coronary outcome. The drinking pattern had animportant effect, with the lowest relative risks among men whoconsumed alcohol three or more days per week, even if the amountconsumed per drinking day was small to moderate.
Episodic consumption of large amounts of alcohol has been associatedwith a high risk of coronary heart disease in several studies.5,6,7,15,16For example, in the Australian World Health Organization MONICA(Monitoring of Trends and Determinants in Cardiovascular Disease)project, men who consumed nine or more drinks per drinking day,as compared with those who did not drink at all, had odds ratiosfor acute myocardial infarction of approximately 2 even if theydrank only one to two days per week, whereas men who consumedone to two drinks on five to six drinking days per week hadan odds ratio of 0.36.6 In contrast, our results emphasize thefrequency of alcohol consumption as the primary determinantof its inverse association with the risk of myocardial infarction.Our results concur with the findings of one meta-analysis ofalcohol consumption and nonfatal myocardial infarction17: anaverage consumption of more than a single drink every two daysoffered only a small incremental benefit. The inverse associationbetween recent alcohol exposure and the risk of myocardial infarction,6,18though debated,19 also offers evidence in support of a benefitof frequent consumption.
Studies differ on whether the drinking pattern modifies high-densitylipoprotein cholesterol levels.5,20,21 The drinking patterndoes not clearly influence fibrinogen levels,22 but it may havean important effect on blood pressure.23,24,25 The Intersaltstudy found that a highly variable pattern of alcohol consumptionpredicted a high mean blood-pressure level among heavy drinkers,regardless of the amount of alcohol consumed in the 24 hoursbefore measurement.26 Likewise, platelet aggregability appearsto be lower among moderate drinkers than among those who didnot drink27 but higher during withdrawal among heavy users ofalcohol.28
When we used two methods of assessing alcohol consumption —at base line and updated every four years during follow-up —we found a stronger association with myocardial infarction forthe updated reports. Because alcohol use changes over time,updating this information should improve the accuracy of assessmentduring the follow-up period, an important feature for exposureswith short-term effects on risk.
We found the strongest associations between alcohol consumptionand the risk of myocardial infarction for beer and liquor, thepredominant types of alcoholic beverages consumed by this population.Our findings support the hypothesis that the beverage most widelyconsumed by a given population is the one most likely to beinversely associated with the risk of myocardial infarctionin that population.29 This may occur because heavily consumedbeverages are more likely to be consumed frequently, as confirmedby their closer correlation with the frequency of drinking inour analyses. The fact that multivariate adjustment strengthenedthe inverse associations of myocardial infarction with beerand liquor but weakened the associations with red wine and whitewine suggests that uncontrolled confounding may explain thegreater benefits attributed to red wine in some studies.30,31
Few studies have assessed increases in alcohol consumption andthe risk of myocardial infarction. In three studies, increasedconsumption over time was associated with a decrease in therisk of subsequent cardiovascular events of a magnitude similarto that in our study,32,33,34 although one study found no significantdifference in the rate of death from coronary or cardiovascularcauses.34 Since advising patients at high risk for myocardialinfarction to drink moderately is controversial, the findingthat a moderate increase in consumption over time appears beneficialmay inform this debate.
Recent reviews suggest that alcohol consumption is mainly associatedwith a decreased risk of myocardial infarction among men over45 years of age and women over 55 years of age.35 We found thatfrequent drinking was associated with a decreased risk evenamong men 40 to 49 years of age who had previously had stablelevels of consumption, implying that this association is notlimited to adults over a specific age. However, the absolutebenefits of moderate drinking will be most apparent among olderadults at increased risk for myocardial infarction, whereasmany of the risks of alcohol consumption, such as trauma, areof paramount concern for younger persons. For example, amongthe middle-aged healthy men in our study, the incidence of myocardialinfarction among those who abstained was 420 cases per 100,000person-years, yielding a difference in risk associated withfrequent alcohol use of approximately 145 cases per 100,000person-years. In younger populations at decreased risk for myocardialinfarction, the difference in risk associated with frequentalcohol use would be smaller.
Although differences among participants in factors other thanalcohol consumption could influence our findings, we found littleadditional confounding by diet, exercise, body-mass index, familyhistory, aspirin use or nonuse, or the presence or absence ofhypertension and diabetes after we controlled for age and smokingstatus, and our population was homogeneous, by design, withrespect to occupational class and sex. In order to have producedthese results, any uncontrolled confounder would need to beassociated with both exposure and the outcome and unrelatedto the covariates included. Our exclusion of former drinkers,the elimination of myocardial infarctions that occurred earlyin the follow-up period, and the similarity in risk among thosewho abstained and those who were very light drinkers argue againstthe "sick quitter" hypothesis36 as an explanation for our findings.
Our ability to separate the associations of the quantity andthe frequency of alcohol consumption with the risk of myocardialinfarction was limited, because the two were correlated. Also,only 3.5 percent of study participants reported consumptionof 50 g or more of alcohol daily, a fact that limited our abilityto study the detrimental effects of heavy drinking.
National guidelines recommend caution when applying the resultsof epidemiologic studies of alcohol consumption to individualpatients, since clinical care requires consideration of themyriad health effects of alcohol and of individual susceptibilityto those effects.35,37 We encourage adults to discuss alcoholuse with their physicians and together make individualized decisionsabout appropriate consumption.
Supported by grants (AA00299, AA11181, HL35464, and CA55075)from the National Institutes of Health.
A portion of this work was presented in abstract form at the2001 Congress of Epidemiology, Toronto, June 13, 2001, and publishedin the American Journal of Epidemiology (2001;153:Suppl:S59).
Dr. Rimm reports having received speaking fees from the DistilledSpirits Council and Beverage Wholesalers.
Source Information
From the Divisions of General Medicine and Primary Care (K.J.M.) and Cardiology (M.A.M.), Beth Israel Deaconess Medical Center, Boston; the Department of Public Health and Community Medicine and the Department of Medicine, University of Sydney, Sydney, New South Wales, Australia (K.M.C.); the Departments of Epidemiology (M.A.M., C.A.C., M.J.S., W.C.W., E.B.R.) and Nutrition (M.J.S., W.C.W., E.B.R.), Harvard School of Public Health, Boston; the Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston (C.A.C., M.J.S., W.C.W., E.B.R.); and the Department of Emergency Medicine, Massachusetts General Hospital, Boston (C.A.C.).
Address reprint requests to Dr. Mukamal at the Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, 330 Brookline Ave., LY-303, Boston, MA 02215, or at kmukamal{at}caregroup.harvard.edu.
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Alcohol and Coronary Heart Disease
Duggirala M. K., Bridges C. M., McLeod T. G., Lieber C. S., Lowenfels A. B., Di Castelnuovo A., Iacoviello L., de Gaetano G., Mukamal K. J., Rimm E. B., Goldberg I. J.
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